17alpha-methyl-17beta-hydroxyestran-3-one



United States Patent 17a-METHYL-17fi-HYDROXYESTRAN-3-ONE Frank B. Colton, Chicago, IlL, as'signor to G. D. Searle & Co., Chicago, 11L, a corporation of Delaware No Drawing. Application March 31, 1958 Serial No. 724,886

1 Claim. (Cl. 260-3974) The present invention relates to a new hormonal agent, and, more particularly to 17u-methy1-17/3-hydroxyestran- 3-one. This product is a hypo-tensive agent and a desoxycorticosterone inhibitor. It inhibits not only the hypertensive but also the sodium retaining efiects of that mineralocorticoid hormone. It is unlike its higher homologs, e.g. the flea-propyl-17,3-hydroxyestran-3-one, in being a potent anabolic agent and in lacking progesta-tional activity. Its hypotensive activity was surprising in view of the inactivity of such related compounds as 17-methyl-19-nortestosterone and 17,6-hydroxyestran-3-one. The compound has minimal androgenic and other undesirable side effects.

The preparation can be conveniently accomplished by the following procedure. To a solution of 1 gram of 17-methyl-l9-nortestosterone in 50 cc. of dioxane are added 0.2 grams of a 5% palladium-on-charcoal catalyst. The mixture is maintained at room temperature in a hydrogen atmosphere until one mole of hydrogen has been absorbed. The solution is then filtered. The filtrate is concentrated under vacuum and the residue is recrystallized from a mixture of acetone and petroleum ether to yield 17a-methyl-17fi-hydroxy-5fi-cstran-3-one oi the structural formula 7 (IJHI The compound melts at about 1365-1375 C.

To isolate the SB-isomer, the filtrate from the crystallization is taken to dryness and the residue is taken up in a solution consisting of petroleum ether and 50% of benzene and thus applied to a chromatography column containing 15% magnesia and silica gel.

The column is eluted with a benzene solution containing 50% petroleum ether and there is thus eluted an additional quantity of the foregoing product. Elution with pure benzene yields a mixture of the Seaand 5pisomers. Further elusion with a solution containing 5% ether in benzene yields the pure l7a methyl-l7fi-hydroxy- Sou-estran-B-one which melts at about l47 C.

The present invention is a continuation-in-part of copending application Serial No. 630,042, filed December 24, 1956, now abandoned.

What is claimed is:

A compound having the formula:

References Cited in the file of this patent UNITED STATES PATENTS 2,308,835 Ruzicka et a1. Ian. 19, 1943 2,845,381 Tindall July 29, 1958 

